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Product listing: c-Raf (D4B3J) Rabbit mAb, UniProt ID P04049 #53745 to Phospho-Syk (Tyr525/526) Antibody, UniProt ID P43405 #2711

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: A-Raf, B-Raf, and c-Raf (Raf-1) are the main effectors recruited by GTP-bound Ras to activate the MEK-MAP kinase pathway (1). Activation of c-Raf is the best understood and involves phosphorylation at multiple activating sites including Ser338, Tyr341, Thr491, Ser494, Ser497, and Ser499 (2). p21-activated protein kinase (PAK) has been shown to phosphorylate c-Raf at Ser338, and the Src family phosphorylates Tyr341 to induce c-Raf activity (3,4). Ser338 of c-Raf corresponds to similar sites in A-Raf (Ser299) and B-Raf (Ser445), although this site is constitutively phosphorylated in B-Raf (5). Inhibitory 14-3-3 binding sites on c-Raf (Ser259 and Ser621) can be phosphorylated by Akt and AMPK, respectively (6,7). While A-Raf, B-Raf, and c-Raf are similar in sequence and function, differential regulation has been observed (8). Of particular interest, B-Raf contains three consensus Akt phosphorylation sites (Ser364, Ser428, and Thr439) and lacks a site equivalent to Tyr341 of c-Raf (8,9). Research studies have shown that the B-Raf mutation V600E results in elevated kinase activity and is commonly found in malignant melanoma (10). Six residues of c-Raf (Ser29, Ser43, Ser289, Ser296, Ser301, and Ser642) become hyperphosphorylated in a manner consistent with c-Raf inactivation. The hyperphosphorylation of these six sites is dependent on downstream MEK signaling and renders c-Raf unresponsive to subsequent activation events (11).

$303
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse

Application Methods: Western Blotting

Background: Autophagy is a catabolic process for the autophagosomic-lysosomal degradation of proteins activated in response to nutrient deprivation and in neurodegenerative conditions (1). One of the proteins critical to this process is Beclin-1, the mammalian orthologue of the yeast autophagy protein Apg6/Vps30 (2). Beclin-1 can complement defects in yeast autophagy caused by loss of Apg6 and can also stimulate autophagy when overexpressed in mammalian cells (3). Mammalian Beclin-1 was originally isolated in a yeast two-hybrid screen for Bcl-2 interacting proteins and has been shown to interact with Bcl-2 and Bcl-xL, but not with Bax or Bak (4). While Beclin-1 is generally ubiquitously expressed, research studies have shown it is monoallelically deleted in 40-75% of sporadic human breast and ovarian cancers (5). Beclin-1 is localized within cytoplasmic structures including the mitochondria, although overexpression of Beclin-1 reveals some nuclear staining and CRM1-dependent nuclear export (6). Investigators have demonstrated that Beclin-1-/- mice die early in embryogenesis and Beclin-1-/+ mice have a high incidence of spontaneous tumors. Stem cells from the null mice demonstrate an altered autophagic response, although responses to apoptosis appeared normal (7). Researchers have also found that overexpression of Beclin-1 in virally infected neurons in vivo resulted in significant protection against Sindbis virus-induced disease and neuronal apoptosis (4).

$303
100 µl
$717
300 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Western Blotting

Background: The epidermal growth factor (EGF) receptor is a transmembrane tyrosine kinase that belongs to the HER/ErbB protein family. Ligand binding results in receptor dimerization, autophosphorylation, activation of downstream signaling, internalization, and lysosomal degradation (1,2). Phosphorylation of EGF receptor (EGFR) at Tyr845 in the kinase domain is implicated in stabilizing the activation loop, maintaining the active state enzyme, and providing a binding surface for substrate proteins (3,4). c-Src is involved in phosphorylation of EGFR at Tyr845 (5). The SH2 domain of PLCγ binds at phospho-Tyr992, resulting in activation of PLCγ-mediated downstream signaling (6). Phosphorylation of EGFR at Tyr1045 creates a major docking site for the adaptor protein c-Cbl, leading to receptor ubiquitination and degradation following EGFR activation (7,8). The GRB2 adaptor protein binds activated EGFR at phospho-Tyr1068 (9). A pair of phosphorylated EGFR residues (Tyr1148 and Tyr1173) provide a docking site for the Shc scaffold protein, with both sites involved in MAP kinase signaling activation (2). Phosphorylation of EGFR at specific serine and threonine residues attenuates EGFR kinase activity. EGFR carboxy-terminal residues Ser1046 and Ser1047 are phosphorylated by CaM kinase II; mutation of either of these serines results in upregulated EGFR tyrosine autophosphorylation (10).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: Carnitine palmitoyltransferase-1 (CPT1), localized to the mitochondrial outer membrane, translocates fatty acids across the mitochondrial membranes and catalyzes the rate-limiting step of β-oxidation (1, 2). There are three isoforms of this enzyme: CPT1A (liver), CPT1B (muscle), and CPT1C (brain) (1, 2). Deficiency of CPT1A results in an autosomal recessive mitochondrial fatty acid oxidation disorder (3). Studies have shown that physiological high blood glucose and insulin levels inhibit CPT1B activity in human muscle and therefore divert long-chain fatty acids toward storage in human muscle as triglycerides (4). Furthermore, mice deficient in CPT1C show less food intake and reduced body weight (5). These findings suggest that CPT1 may play a role in metabolic syndromes.

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Flow Cytometry, Immunofluorescence (Immunocytochemistry), Immunohistochemistry (Paraffin), Immunoprecipitation, Western Blotting

Background: Nucleolin is a multi-functional protein that is one of the major components of the nucleoli (1). Nucleolin plays an essential role in various steps of ribosome biogenesis including rRNA synthesis, processing of pre-rRNA, pre-ribosomal RNA assembly, and transport of ribosomal proteins out of the nucleus (1-3). While the main function of nucleolin is ribosome biogenesis, it plays an important role in various other nuclear activities. Down regulation of nucleolin leads to increased expression of p53, defects in genome duplication, and a delay at prometaphase during mitosis leading to cell cycle arrest (4-6). In addition, nucleolin has been found in a complex with Rad51 and may participate in DNA repair by homologous recombination (7). Nucleolin binds to the catalytic subunit of the human telomerase reverse transcriptase, hTERT, and is thought to be involved in telomere maintenance (8). Nucleolin also possesses histone chaperone activity and is able to enhance the chromatin remodeling efficiency of SWItch/Sucrose Non Fermentable (SWI/SNF) and ATP-dependent chromatin-assembly factor (ACF), remove histone H2A-H2B dimers from nucleosomes, and facilitate the passage of RNA polymerase through chromatin (9).

$122
20 µl
$303
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Phosphoinositide-dependent protein kinase 1 (PDK1) plays a central role in many signal transduction pathways (1,2) including the activation of Akt and the PKC isoenzymes p70 S6 kinase and RSK (3). Through its effects on these kinases, PDK1 is involved in the regulation of a wide variety of processes, including cell proliferation, differentiation and apoptosis.

$303
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Chromatin IP, Flow Cytometry, Immunofluorescence (Immunocytochemistry), Immunoprecipitation, Western Blotting

Background: The nucleosome, made up of four core histone proteins (H2A, H2B, H3, and H4), is the primary building block of chromatin. Originally thought to function as a static scaffold for DNA packaging, histones have now been shown to be dynamic proteins, undergoing multiple types of post-translational modifications, including acetylation, phosphorylation, methylation, and ubiquitination (1,2). Histone acetylation occurs mainly on the amino-terminal tail domains of histones H2A (Lys5), H2B (Lys5, 12, 15, and 20), H3 (Lys9, 14, 18, 23, 27, 36 and 56), and H4 (Lys5, 8, 12, and 16) and is important for the regulation of histone deposition, transcriptional activation, DNA replication, recombination, and DNA repair (1-3). Hyper-acetylation of the histone tails neutralizes the positive charge of these domains and is believed to weaken histone-DNA and nucleosome-nucleosome interactions, thereby destabilizing chromatin structure and increasing the accessibility of DNA to various DNA-binding proteins (4,5). In addition, acetylation of specific lysine residues creates docking sites for a protein module called the bromodomain, which binds to acetylated lysine residues (6). Many transcription and chromatin regulatory proteins contain bromodomains and may be recruited to gene promoters, in part, through binding of acetylated histone tails. Histone acetylation is mediated by histone acetyltransferases (HATs), such as CBP/p300, GCN5L2, PCAF, and Tip60, which are recruited to genes by DNA-bound protein factors to facilitate transcriptional activation (3). Deacetylation, which is mediated by histone deacetylases (HDAC and sirtuin proteins), reverses the effects of acetylation and generally facilitates transcriptional repression (7,8).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Upon activation by Janus kinases, Stat6 translocates to the nucleus where it regulates cytokine-induced gene expression. Stat6 is activated via phosphorylation at Tyr641 and is required for responsiveness to IL-4 and IL-13 (1-4). In addition, Stat6 is activated by IFN-α in B cells, where it forms transcriptionally active complexes with Stat2 and p48 (5,6). Protein phosphatase 2A is also involved in regulation of IL-4-mediated Stat6 signaling (7).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Immunofluorescence (Immunocytochemistry), Western Blotting

Background: The polycomb group (PcG) proteins are involved in maintaining the silenced state of several developmentally regulated genes and contribute to the maintenance of cell identity, cell cycle regulation, and oncogenesis (1,2). Enhancer of zeste homolog 2 (Ezh2), a member of this large protein family, contains four conserved regions including domain I, domain II, and a cysteine-rich amino acid stretch that precedes the carboxy-terminal SET domain (3). The SET domain has been linked with histone methyltransferase (HMTase) activity. Moreover, mammalian Ezh2 is a member of a histone deacetylase complex that functions in gene silencing, acting at the level of chromatin structure (4). Ezh2 complexes methylate histone H3 at Lys9 and 27 in vitro, which is thought to be involved in targeting transcriptional regulators to specific loci (5). Ezh2 is deregulated in various tumor types, and its role, both as a primary effector and as a mediator of tumorigenesis, has become a subject of increased interest (6).

$122
20 µl
$293
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Immunofluorescence (Immunocytochemistry), Immunoprecipitation, Western Blotting

Background: Clathrin-coated vesicles provide for the intracellular transport of cargo proteins following endocytosis and during multiple vesicle trafficking pathways. Vesicles form at specialized areas of the cell membrane where clathrin and associated proteins form clathrin-coated pits. Invagination of these cell membrane-associated pits internalizes proteins and forms an intracellular clathrin-coated vesicle (1,2). Clathrin is the most abundant protein in these vesicles and is present as a basic assembly unit called a triskelion. Each clathrin triskelion is composed of three clathrin heavy chains and three clathrin light chains. Clathrin heavy chain proteins are composed of several functional domains, including a carboxy-terminal region that permits interaction with other heavy chain proteins within a triskelion, and a globular amino-terminal region that associates with other vesicle proteins (2). Adaptor proteins, such as AP2, epsin and EPS15, are responsible for the recruitment of vesicle proteins to sites of pit formation and the assembly of the clathrin-coated vesicle. Following vesicle invagination, the GTPase dynamin constricts the neck of the nascent vesicle to complete formation of the free, cytosolic vesicle (3,4).

PhosphoPlus® Duets from Cell Signaling Technology (CST) provide a means to assess protein activation status. Each Duet contains an activation-state and total protein antibody to your target of interest. These antibodies have been selected from CST's product offering based upon superior performance in specified applications.

Background: The stress-activated protein kinase/Jun-amino-terminal kinase SAPK/JNK is potently and preferentially activated by a variety of environmental stresses including UV and gamma radiation, ceramides, inflammatory cytokines, and in some instances, growth factors and GPCR agonists (1-6). As with the other MAPKs, the core signaling unit is composed of a MAPKKK, typically MEKK1-MEKK4, or by one of the mixed lineage kinases (MLKs), which phosphorylate and activate MKK4/7. Upon activation, MKKs phosphorylate and activate the SAPK/JNK kinase (2). Stress signals are delivered to this cascade by small GTPases of the Rho family (Rac, Rho, cdc42) (3). Both Rac1 and cdc42 mediate the stimulation of MEKKs and MLKs (3). Alternatively, MKK4/7 can be activated in a GTPase-independent mechanism via stimulation of a germinal center kinase (GCK) family member (4). There are three SAPK/JNK genes each of which undergoes alternative splicing, resulting in numerous isoforms (3). SAPK/JNK, when active as a dimer, can translocate to the nucleus and regulate transcription through its effects on c-Jun, ATF-2, and other transcription factors (3,5).

$303
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunofluorescence (Immunocytochemistry), Western Blotting

Background: The receptor-interacting protein (RIP) family of serine-threonine kinases (RIP, RIP2, RIP3, and RIP4) are important regulators of cellular stress that trigger pro-survival and inflammatory responses through the activation of NF-κB, as well as pro-apoptotic pathways (1). In addition to the kinase domain, RIP contains a death domain responsible for interaction with the death domain receptor Fas and recruitment to TNF-R1 through interaction with TRADD (2,3). RIP-deficient cells show a failure in TNF-mediated NF-κB activation, making the cells more sensitive to apoptosis (4,5). RIP also interacts with TNF-receptor-associated factors (TRAFs) and can recruit IKKs to the TNF-R1 signaling complex via interaction with NEMO, leading to IκB phosphorylation and degradation (6,7). Overexpression of RIP induces both NF-κB activation and apoptosis (2,3). Caspase-8-dependent cleavage of the RIP death domain can trigger the apoptotic activity of RIP (8).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse

Application Methods: Flow Cytometry, Peptide ELISA (DELFIA), Western Blotting

Background: Interferon-stimulated 15 kDa protein (ISG15), also known as ubiquitin cross-reactive protein (UCRP), is a member of the ubiquitin-like protein family and functions in various biological pathways from pregnancy to innate immune responses (1). Expression of ISG15 is stimulated by cellular exposure to type 1 interferons α and β, in addition to infection with viruses such as influenza B (2,3). After exposure to type I interferons, both lymphocytes and monocytes, in addition to some fibroblasts and epithelial cells, release ISG15 into culture medium (1,4). ISG15 has been shown to function as a cytokine, stimulating interferon γ secretion by monocytes and macrophages, proliferation of natural killer cells, and chemotactic responses in neutrophils (4,5). ISG15 has also been shown to function intracellularly, being covalently conjugated to other proteins by E1 (Ube1L), E2 (UbcH8) and E3 ligases via a multi-step process analogous to ubiquitination (6,7). ISG15 is removed from proteins by the ubiquitin processing protease Ubp43 (8). ISG15-protein conjugation (ISGylation) is induced by type 1 interferons, and target proteins include the serine protease inhibitor Serpin 2A, PLCγ1, ERK1/2, Jak1 and Stat1 (9,10). Unlike ubiquitination, ISGylation does not target proteins for degradation, rather ISGylation increases Jak1 and Stat1 activity, enhancing the cellular response to interferons (11).

$303
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: Ataxia telangiectasia mutated kinase (ATM) and ataxia telangiectasia and Rad3-related kinase (ATR) are PI3 kinase-related kinase (PIKK) family members that phosphorylate multiple substrates on serine or threonine residues that are followed by a glutamine in response to DNA damage or replication blocks (1-3). Despite the essential role of ATR in cell cycle signaling and DNA repair processes, little is known about its activation. ATR was long thought to exist in a constitutively active state in cells, with DNA damage-induced signaling occurring via recruitment of ATR to single stranded DNA and sites of replication stress. Phosphorylation of ATR at serine 428 in response to UV-induced DNA damage has been suggested as a means of activating ATR (4,5). Recent work has shown autophosphorylation of ATR at threonine 1989. Like ATM Ser1981, phosphorylation of ATR Thr1989 occurs in response to DNA damage, indicating that phosphorylation at this site is important in ATR-mediated signaling (6,7).

PhosphoPlus® Duets from Cell Signaling Technology (CST) provide a means to assess protein activation status. Each Duet contains an activation-state and total protein antibody to your target of interest. These antibodies have been selected from CST's product offering based upon superior performance in specified applications.

Background: The epidermal growth factor (EGF) receptor is a transmembrane tyrosine kinase that belongs to the HER/ErbB protein family. Ligand binding results in receptor dimerization, autophosphorylation, activation of downstream signaling, internalization, and lysosomal degradation (1,2). Phosphorylation of EGF receptor (EGFR) at Tyr845 in the kinase domain is implicated in stabilizing the activation loop, maintaining the active state enzyme, and providing a binding surface for substrate proteins (3,4). c-Src is involved in phosphorylation of EGFR at Tyr845 (5). The SH2 domain of PLCγ binds at phospho-Tyr992, resulting in activation of PLCγ-mediated downstream signaling (6). Phosphorylation of EGFR at Tyr1045 creates a major docking site for the adaptor protein c-Cbl, leading to receptor ubiquitination and degradation following EGFR activation (7,8). The GRB2 adaptor protein binds activated EGFR at phospho-Tyr1068 (9). A pair of phosphorylated EGFR residues (Tyr1148 and Tyr1173) provide a docking site for the Shc scaffold protein, with both sites involved in MAP kinase signaling activation (2). Phosphorylation of EGFR at specific serine and threonine residues attenuates EGFR kinase activity. EGFR carboxy-terminal residues Ser1046 and Ser1047 are phosphorylated by CaM kinase II; mutation of either of these serines results in upregulated EGFR tyrosine autophosphorylation (10).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: The Stat1 transcription factor is activated in response to a large number of ligands (1) and is essential for responsiveness to IFN-α and IFN-γ (2,3). Phosphorylation of Stat1 at Tyr701 induces Stat1 dimerization, nuclear translocation, and DNA binding (4). Stat1 protein exists as a pair of isoforms, Stat1α (91 kDa) and the splice variant Stat1β (84 kDa). In most cells, both isoforms are activated by IFN-α, but only Stat1α is activated by IFN-γ. The inappropriate activation of Stat1 occurs in many tumors (5). In addition to tyrosine phosphorylation, Stat1 is also phosphorylated at Ser727 through a p38 mitogen-activated protein kinase (MAPK)-dependent pathway in response to IFN-α and other cellular stresses (6). Serine phosphorylation may be required for the maximal induction of Stat1-mediated gene activation.

The HER/ErbB Family Antibody Sampler Kit provides an economical means to evaluate the HER/ErbB Family, including the phosphorylation of EGFR, HER2/ErbB2, HER3/ErbB3, and HER4/ErbB4. The control antibodies to each family member are also included. The kit contains enough antibody to perform two western blot experiments with each primary antibody.
$260
100 µl
APPLICATIONS
REACTIVITY
Bovine, Human, Monkey, Mouse, Pig, Rat

Application Methods: Western Blotting

Background: The 14-3-3 family of proteins plays a key regulatory role in signal transduction, checkpoint control, apoptotic and nutrient-sensing pathways (1,2). 14-3-3 proteins are highly conserved and ubiquitously expressed. There are at least seven isoforms, β, γ, ε, σ, ζ, τ, and η that have been identified in mammals. The initially described α and δ isoforms are confirmed to be phosphorylated forms of β and ζ, respectively (3). Through their amino-terminal α helical region, 14-3-3 proteins form homo- or heterodimers that interact with a wide variety of proteins: transcription factors, metabolic enzymes, cytoskeletal proteins, kinases, phosphatases, and other signaling molecules (3,4). The interaction of 14-3-3 proteins with their targets is primarily through a phospho-Ser/Thr motif. However, binding to divergent phospho-Ser/Thr motifs, as well as phosphorylation independent interactions has been observed (4). 14-3-3 binding masks specific sequences of the target protein, and therefore, modulates target protein localization, phosphorylation state, stability, and molecular interactions (1-4). 14-3-3 proteins may also induce target protein conformational changes that modify target protein function (4,5). Distinct temporal and spatial expression patterns of 14-3-3 isoforms have been observed in development and in acute response to extracellular signals and drugs, suggesting that 14-3-3 isoforms may perform different functions despite their sequence similarities (4). Several studies suggest that 14-3-3 isoforms are differentially regulated in cancer and neurological syndromes (2,3).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Chromatin IP, Chromatin IP-seq, Immunofluorescence (Immunocytochemistry), Immunoprecipitation, Western Blotting

Background: ETS-1 is a proto-oncoprotein that belongs to the E26 Transformation-specific Sequence (ETS) family of transcription factors that share a unique and highly conserved DNA binding domain (1). ETS-1 plays important roles in vascular development and angiogenesis (2), and vascular inflammation and remodeling (3). The target genes of ETS-1 include receptor tyrosine kinases, MMPs, and cell adhesion molecules (4-6). In addition, ETS-1 is involved in regulation of energy metabolism in cancer cells (7). ETS-1 activity is regulated by two different types of phosphorylation sites. While phosphorylation at a cluster of serine residues in the exon VII domain by CaMKII inhibits ETS-1 DNA binding activity (8), phosphorylation at its Thr38 site by Ras activates ETS-1 (9).

$327
50 tests
100 µl
This Cell Signaling Technology antibody is conjugated to Alexa Fluor® 488 fluorescent dye and tested in-house for direct flow cytometry and immunofluorescent analysis in human cells. This antibody is expected to exhibit the same species cross-reactivity as the unconjugated Tri-Methyl-Histone H3 (Lys27) (C36B11) Rabbit mAb #9733.
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Flow Cytometry, Immunofluorescence (Immunocytochemistry)

Background: The nucleosome, made up of four core histone proteins (H2A, H2B, H3, and H4), is the primary building block of chromatin. Originally thought to function as a static scaffold for DNA packaging, histones have now been shown to be dynamic proteins, undergoing multiple types of post-translational modifications, including acetylation, phosphorylation, methylation, and ubiquitination (1). Histone methylation is a major determinant for the formation of active and inactive regions of the genome and is crucial for the proper programming of the genome during development (2,3). Arginine methylation of histones H3 (Arg2, 17, 26) and H4 (Arg3) promotes transcriptional activation and is mediated by a family of protein arginine methyltransferases (PRMTs), including the co-activators PRMT1 and CARM1 (PRMT4) (4). In contrast, a more diverse set of histone lysine methyltransferases has been identified, all but one of which contain a conserved catalytic SET domain originally identified in the Drosophila Su(var)3-9, Enhancer of zeste, and Trithorax proteins. Lysine methylation occurs primarily on histones H3 (Lys4, 9, 27, 36, 79) and H4 (Lys20) and has been implicated in both transcriptional activation and silencing (4). Methylation of these lysine residues coordinates the recruitment of chromatin modifying enzymes containing methyl-lysine binding modules such as chromodomains (HP1, PRC1), PHD fingers (BPTF, ING2), tudor domains (53BP1), and WD-40 domains (WDR5) (5-8). The discovery of histone demethylases such as PADI4, LSD1, JMJD1, JMJD2, and JHDM1 has shown that methylation is a reversible epigenetic marker (9).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: CRBN/Cereblon, a substrate receptor for the CRL4 E3 ubiquitin ligase, was originally identified for its role in autosomal recessive nonsyndromic mental retardation (1). CRBN’s role in the regulation of the AMPK pathway has been linked to various human diseases, including cardiovascular disease and obesity, and its involvement in proteasomal degradation may be important in neuropsychiatric diseases (2). CRBN has also been shown to enhance the effects of immunomodulatory drugs (IMiDs) in multiple myeloma, and may be a predictive marker for therapy (2-4).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Chromatin IP, Flow Cytometry, Immunofluorescence (Immunocytochemistry), Immunohistochemistry (Paraffin), Immunoprecipitation, Western Blotting

Background: Lysine-specific demethylase 1 (LSD1; also known as AOF2 and BHC110) is a nuclear amine oxidase homolog that acts as a histone demethylase and transcription cofactor (1). Gene activation and repression is specifically regulated by the methylation state of distinct histone protein lysine residues. For example, methylation of histone H3 at Lys4 facilitates transcriptional activation by coordinating the recruitment of BPTF, a component of the NURF chromatin remodeling complex, and WDR5, a component of multiple histone methyltransferase complexes (2,3). In contrast, methylation of histone H3 at Lys9 facilitates transcriptional repression by recruiting HP1 (4,5). LSD1 is a component of the CoREST transcriptional co-repressor complex that also contains CoREST, CtBP, HDAC1 and HDAC2. As part of this complex, LSD1 demethylates mono-methyl and di-methyl histone H3 at Lys4 through a FAD-dependent oxidation reaction to facilitate neuronal-specific gene repression in non-neuronal cells (1,6,7). In contrast, LSD1 associates with androgen receptor in human prostate cells to demethylate mono-methyl and di-methyl histone H3 at Lys9 and facilitate androgen receptor-dependent transcriptional activation (8). Therefore, depending on gene context LSD1 can function as either a transcriptional co-repressor or co-activator. LSD1 activity is inhibited by the amine oxidase inhibitors pargyline, deprenyl, clorgyline and tranylcypromine (8).

$303
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunofluorescence (Immunocytochemistry), Immunohistochemistry (Paraffin), Immunoprecipitation, Western Blotting

Background: Paired box (PAX) proteins are a family of transcription factors that play important and diverse roles in animal development (1). Nine PAX proteins (PAX1-9) have been described in humans and other mammals. They are defined by the presence of an amino-terminal "paired" domain, consisting of two helix-turn-helix motifs, with DNA binding activity (2). PAX proteins are classified into four structurally distinct subgroups (I-IV) based on the absence or presence of a carboxy-terminal homeodomain and a central octapeptide region. Subgroup I (PAX1 and 9) contains the octapeptide but lacks the homeodomain; subgroup II (PAX2, 5, and 8) contains the octapeptide and a truncated homeodomain; subgroup III (PAX3 and 7) contains the octapeptide and a complete homeodomain; and subgroup IV (PAX4 and 6) contains a complete homeodomain but lacks the octapeptide region (2). PAX proteins play critically important roles in development by regulating transcriptional networks responsible for embryonic patterning and organogenesis (3); a subset of PAX proteins also maintain functional importance during postnatal development (4). Research studies have implicated genetic mutations that result in aberrant expression of PAX genes in a number of cancer subtypes (1-3), with members of subgroups II and III identified as potential mediators of tumor progression (2).

$195
1 units
The Magnetic Separation Rack is designed for quick and easy small-scale isolation of immunocomplexes from chromatin immunoprecipitations (ChIP assays) using SimpleChIP® Enzymatic Chromatin IP Kit (Magnetic Beads) #9003 or ChIP-Grade Protein G Magnetic Beads #9006. The rack holds up to six 1.5-2.0 ml tubes and contains three neodymium rare earth permanent magnets. Rare earth magnets are extremely powerful and should be kept away from mechanical/electrical instruments which may be damaged by high magnetic fields.
APPLICATIONS

Application Methods: Chromatin IP, Immunoprecipitation

$111
20 µl
$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Insulin receptor substrate 1 (IRS-1) is one of the major substrates of the insulin receptor kinase (1). IRS-1 contains multiple tyrosine phosphorylation motifs that serve as docking sites for SH2-domain containing proteins that mediate the metabolic and growth-promoting functions of insulin (2-4). IRS-1 also contains over 30 potential serine/threonine phosphorylation sites. Ser307 of IRS-1 is phosphorylated by JNK (5) and IKK (6) while Ser789 is phosphorylated by SIK-2, a member of the AMPK family (7). The PKC and mTOR pathways mediate phosphorylation of IRS-1 at Ser612 and Ser636/639, respectively (8,9). Phosphorylation of IRS-1 at Ser1101 is mediated by PKCθ and results in an inhibition of insulin signaling in the cell, suggesting a potential mechanism for insulin resistance in some models of obesity (10).

$122
20 µl
$293
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunofluorescence (Frozen), Immunohistochemistry (Paraffin), Immunoprecipitation, Western Blotting

Background: Calcium-binding proteins of different subfamilies regulate the second messenger calcium. Calbindin, calmodulin, S-100, parvalbumin and troponin C are members of the low molecular weight calcium-binding protein family (1). Calbindin is expressed in discrete neuronal populations within the CNS and is thought to act as an intracellular calcium buffering protein. Most Purkinje cells express calbindin, which is expressed when neurons start to migrate and differentiate. In contrast, other calcium buffering proteins, such as parvalbumin, are expressed later during development and in parallel with increasing neuronal activity (2).

$111
20 µl
$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Chromatin IP, Immunofluorescence (Immunocytochemistry), Western Blotting

Background: G9a, also known as Euchromatic histone-lysine N-methyltransferase 2 (EHMT2), is a member of a family of histone lysine methyltransferases, each of which contains a conserved catalytic SET domain originally identified in Drosophila Su[var]3-9, Enhancer of zeste, and Trithorax proteins (1). Recombinant G9a can mono-, di- and tri-methylate histone H3 on Lys9 and Lys27 in vitro (1,2). However, in vivo G9a forms a complex with GLP, a G9a-related histone methyltransferase, and together these proteins function as the major euchromatic histone H3 Lys9 mono- and di-methyltransferases, creating transcriptionally repressive marks that facilitate gene silencing (3,4). G9a methylates itself on Lys165, a modification that regulates the association of HP1 repressor proteins with the G9a/GLP complex (5). The G9a/GLP complex also contains Wiz, a zinc finger protein that is required for G9a/GLP hetero-dimerization and complex stability (6). Wiz contains two CtBP co-repressor binding sites, which mediate the association of the G9a/GLP with the CtBP co-repressor complex (6). In addition, G9a and GLP are components of other large transcriptional co-repressor complexes, such as those involving E2F6 and CDP/cut (7-9). G9a interacts with DNMT1, and both proteins are required for methylation of DNA and histone H3 (Lys9) at replication foci, providing a functional link between histone H3 Lys9 and CpG methylation during DNA replication (10). G9a activity is critical for meiotic prophase progression, as mutant mice deficient in germ line G9a show a large loss of mature gametes (11). In addition, G9a facilitates increased global levels of di-methyl histone H3 (Lys9) during hypoxic stress and increased G9a expression is associated with hepatocelluar carcinoma (12,13).

$111
20 µl
$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Flow Cytometry, Immunofluorescence (Immunocytochemistry), Immunoprecipitation, Western Blotting

Background: Aurora A (AIK) is a cell cycle-regulated Ser/Thr protein kinase that is overexpressed in many tumor cell lines (1-3). Phosphorylation of Aurora A at Thr288 within the kinase activation loop results in a significant increase in its activity and may target the protein for proteasomal degradation during mitosis (4). The closely-related kinase Aurora B (AIM1) has been implicated in multiple mitotic events (5), and siRNA silencing of Aurora B expression results in reduced histone H3 phosphorylation, aberrant chromosome alignment/segregation, and altered survivin localization (6).

$111
20 µl
$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Cytoplasmic acetyl-CoA synthetase (AceCS1) catalyzes the conversion of acetate and CoA to acetyl-CoA (1, 2). Acetyl-CoA synthesized by AceCS1 is used for fatty acid and lipid biosynthesis (1, 2). Studies suggest that this enzyme is regulated by sterol regulatory element-binding proteins (2). It was also shown that this enzyme is acetylated by protein acetyltransferases in cells (3, 4). SIRT1 deacetylates this enzyme at Lys661 resulting in its activation and the increase of fatty acid synthesis (3, 4).

$303
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: Syk is a protein tyrosine kinase that plays an important role in intracellular signal transduction in hematopoietic cells (1-3). Syk interacts with immunoreceptor tyrosine-based activation motifs (ITAMs) located in the cytoplasmic domains of immune receptors (4). It couples the activated immunoreceptors to downstream signaling events that mediate diverse cellular responses, including proliferation, differentiation, and phagocytosis (4). There is also evidence of a role for Syk in nonimmune cells and investigators have indicated that Syk is a potential tumor suppressor in human breast carcinomas (5). Tyr323 is a negative regulatory phosphorylation site within the SH2-kinase linker region in Syk. Phosphorylation at Tyr323 provides a direct binding site for the TKB domain of Cbl (6,7). Tyr352 of Syk is involved in the association of PLCγ1 (8). Tyr525 and Tyr526 are located in the activation loop of the Syk kinase domain; phosphorylation at Tyr525/526 of human Syk (equivalent to Tyr519/520 of mouse Syk) is essential for Syk function (9).